title: Ca2+ entry through cardiac L-type Ca2+ channels modulates beta-adrenergic stimulation in mouse ventricular myocytes.
abstract: beta-adrenergic receptor (beta-AR) stimulation increases cardiac L-type Ca2+ channel (CaCh) currents via cAMP-dependent phosphorylation. We report here that the affinity and maximum response of CaCh to isoproterenol (Iso), in mouse ventricular myocytes were significantly higher when Ba2+ was used as the charge carrier (IBa) instead of Ca2+ (ICa). The EC50 and maximum increase of peak currents were 43.7 +/- 7.9 nM and 1.8 +/- 0.1-fold for ICa and 23.3 +/- 4.7 nM and 2.4 +/- 0.1-fold for IBa. When cells were dialyzed with the faster Ca2+ chelator, BAPTA, both sensitivity and maximum response of ICa to Iso were significantly augmented compared to cells with EGTA (EC50 of 23.1 +/- 5.2 nM and maximal increase of 2.2 +/- 0.1-fold). Response of ICa to forskolin was also significantly increased when cells were dialyzed with BAPTA or when currents were measured in Ba2+. In contrast, depletion of the sarcoplasmic reticulum (SR) Ca2+ stores by ryanodine did not alter sensitivity of ICa to Iso or forskolin. These results suggest that the Ca2+ entering through CaCh regulates cAMP-dependent phosphorylation, and such negative feedback may play a significant role in cellular Ca2+ homeostasis and contraction in cardiac cells during beta-AR stimulation.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sako
authors.forename: N
authors.initials: N
authors.lastname: Sperelakis
authors.forename: A
authors.initials: A
authors.lastname: Yatani
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D016276:Ventricular Function
chemical_list: D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D002614:Chelating Agents; D011943:Receptors, Adrenergic, beta; D012433:Ryanodine; D001464:Barium; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007545:Isoproterenol; D002118:Calcium